Since the advent of molecular imprinting 20 years ago, there are still challenges when imprinting larger than 1,500 Da molecules. The imprinting process is hindered by multiple factors such as: size, molecule complexity, and conformational structure of the template. In addition, the majority of imprinting technologies involve organic solvents. Because of the aggressive synthesis environment, a protein template might denature before an imprint is formed. If the synthesis of molecular imprinted polymers (MIPs) were to occur at an environment where the template were to subsist for as long as the formation of the imprint, however, potentially larger imprints from active biomolecules and antibodies may be fabricated.
Imprinting of larger molecules has long been recognized for its potential to be used in diagnostic devices especially in low resource settings commonly found in many developing countries. Currently, lateral flow assays are used in low-resource settings because of their speed, ease of use, and relative low cost. Unfortunately, these assays have multiple limitations, such as poor sensitivity for many analytes of clinical importance and inability to multiplex. Furthermore, the antibodies used in these devices suffer from product stability, slow and difficult manufacturing, and some require strict cold chain requirements that can be difficult to maintain. These points underscore the significance in developing robust and stable receptor molecules that can mimic biomolecules such as antibodies and enzymes.
As an alternative, MIPs can be used as artificial recognition molecules with the added advantage of rapid manufacturing at any scale. In addition to being used as artificial recognition molecules, MIPs have similar binding strengths as those seen in antibodies, can be stored dry for several years, reused hundreds of times before losing recognition capabilities, and can be rapidly manufactured at any scale. However, the use of MIPs as artificial antibodies is still not a possibility, as immunogenic antigens are typically larger than 6,000 Da. For many putative diagnostic devices, recognition of macromolecules such as 150 kD antibodies is necessary.